Hypercholesterolemia linked to poor prognosis in primary biliary cholangitis

In patients with primary biliary cholangitis (PBC), elevated total cholesterol levels are associated with dysregulation of lipid metabolism and may lead to poor clinical outcomes, as shown in a study.

The study included 531 patients with PBC without prior cirrhosis-related complications. These patients were assigned into the derivation and validation cohorts. Researchers collected and analysed the patients’ clinical data. Untargeted lipidomics was also performed in 89 patients and 28 healthy controls. Study endpoints included liver-related death, liver transplantation, and cirrhosis-related complications.

Total cholesterol at baseline showed an independent association with poor clinical outcomes both in the derivation cohort (adjusted C-statistic, 0.8035, 95 percent confidence interval [CI], 0.7372–0.8470) and the validation cohort (adjusted C-statistic, 0.8754, 95 percent CI, 0.7777–0.9067).

The predictive ability of total cholesterol for disease outcomes remained consistent over the years and was comparable to the Globe score. A total cholesterol cutoff of 5.2 mmol/L was identified as the optimal level for distinguishing between low- and high-risk patient groups. The risk stratification further improved when total cholesterol and Globe score were combined.

Untargeted lipidomics data showed an upregulation of lipids in high-risk patients. In the pathway analysis of 66 upregulated lipids, high-risk patients had dysregulated glycerophospholipid and sphingolipid metabolism, which were associated with poor clinical outcomes.